Among the best known and widely used class of antibacterial agents are the so-called .beta.-lactam antibiotics. These compounds are characterized in that they have a nucleus consisting of a 2-azetidinone (.beta.-lactam) ring. When the .beta.-lactam is fused to a thiazolidine ring, the compounds are usually referred to generically as penicillins. When the .beta.-lactam is fused to a dihydrothiazine ring, the compounds are referred to as cephalosporins.
The .beta.-lactam antibiotics are synthesized, for no apparent reason, by only a few microorganisms. All of the organisms recognized to produce .beta.-lactam antibiotics are filamentous microorganisms, but not all of these microorganisms are taxonomically related. Some are fungi (eukaryotes), whereas others are streptomycetes (prokaryotes). Thienamycin, U.S. Pat. No. 3,950,357, is an interesting new .beta.-lactam antibiotic produced by a species of Streptomyces.
Nocardicin A, U.S. Pat. No. 3,923,977, is a novel .beta.-lactam antibiotic produced by Nocardia uniformis var. tsuyamanensis ATCC 21806. Nocardicin A has an unusual .beta.-lactam moiety which is uniquely different from all other .beta.-lactam antibiotics in not being fused to another ring as shown in the following structure: ##STR1##
The unique structure of nocardicin A may account for its relative stability toward a variety of .beta.-lactamases as well as for its negligible immunological cross-reactivity with penicillins and cephalosporins.
Unfortunately, the outstanding in vitro and in vivo antimicrobial properties of the penicillins and caphalosporins are not shared by nocardicin A. However, the antibiotic's nucleus, 3-aminonocardicinic acid, of the following structure has been prepared, J. Am. Chem. Soc. 100, 3933 (1978): ##STR2##
The present invention is concerned with the discovery that nocardicin A is produced by a new species of Nocardiopsis designated Nocardiopsis atra Huang sp. nov. ATCC 31511. The microorganism with its potential for cultural and mutational development offers promise of the production of large amounts of nocardicin A, subsequent cleavage to 3-aminonocardicinic acid and the synthesis of a variety of clinically useful semisynthetic nocardicins paralleling those of the semisynthetic penicillins and cephalosporins.